The primary research goal of this project is to develop compounds that have potential utility as therapeutic agents for cocaine addiction. The primary objectives are to synthesize and evaluate the in vitro binding affinity of compounds targeted for the dopamine transporter. These compounds are designed to elucidate the mechanism of action of the dopamine transporter. As such, a better understanding of the mechanisms of action of dopamine uptake inhibition may provide leads toward the development of a cocaine therapeutic agent. The specific aims of the proposed research are focused on the study of the SAR of novel analogues of alkylidenyltropane/GBR 12909 hybrid analogues. These studies are designed to explore further the SAR of this novel class of dopamine uptake inhibitors with the aim of developing more potent and more selective analogues. All compounds prepared in this study will be evaluated for dopamine, serotonin and norepinephrine transporter affinity as well as for their ability to inhibit dopamine uptake. The vitro studies will be performed in rat-brain tissue assays in collaboration with researchers in the Department of Psychiatry and Behavioral Sciences, University of Miami.